Background:Liu-Jun-Zi decoction(LJZD),a classical nourishing formula in China,has been proven to be effective in treating chemotherapy-induced anorexia.In this study,the mechanism of LJZD in alleviating chemotherapy-i...Background:Liu-Jun-Zi decoction(LJZD),a classical nourishing formula in China,has been proven to be effective in treating chemotherapy-induced anorexia.In this study,the mechanism of LJZD in alleviating chemotherapy-induced anorexia was discussed from the aspects of regulating gut microbiota,repairing intestinal barrier injury and inhibiting inflammatory pathways.Methods:A rat model of chemotherapy-induced anorexia was established using cisplatin.The study evaluated the therapeutic effects of LJZD by observing the weight,food intake,and intestinal pathology of rats.The impact of LJZD on gut microbiota and metabolites,specifically short-chain fatty acids,was investigated through gut microbiota analysis and targeted metabolomics.The anti-inflammatory and intestinal protective effects of LJZD were assessed by examining the expression of intestinal tight junction proteins associated with the inflammatory pathway.Results:LJZD alleviated cisplatin-induced inflammation and intestinal barrier disruption,as evidenced by upregulated expression of tight junction protein 1(TJ-1)and occludin,along with reduced serum levels of interleukin 6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and lipopolysaccharide.Additionally,LJZD alleviated microbiota imbalance and regulated the levels of short-chain fatty acids,especially increased the relative abundance of Coriobacteriales Incertae Sedis,Lactabacillus johnsonii F19785,Parasutterella,and reduced the Tyzzerella.In the hypothalamus,LJZD exerts suppressive effects on the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)p65 signaling pathway,leading to a downregulation in the transcriptional activity of IL-6 and IL-1β,as well as Interleukin 6 receptors(IL-6R)and Interleukin-1βreceptors(IL-1R1)mRNA expression levels.Conclusion:In summary,LJZD alleviate chemotherapy-induced anorexia by modulating the gut microbiota,repairing the intestinal mechanical barriers,and suppressing the TLR4/MyD88/NF-κB p65 signaling pathway.展开更多
目的探讨白藜芦醇对脑胶质瘤细胞U251的增殖和上皮间质转化(EMT)的影响及对核转录子kappa B p65(NF-κB p65)通路的调节作用。方法将第3代对数生长期U251细胞随机分为对照组、白藜芦醇组、激动剂组和激动剂+白藜芦醇组,对照组细胞不做处...目的探讨白藜芦醇对脑胶质瘤细胞U251的增殖和上皮间质转化(EMT)的影响及对核转录子kappa B p65(NF-κB p65)通路的调节作用。方法将第3代对数生长期U251细胞随机分为对照组、白藜芦醇组、激动剂组和激动剂+白藜芦醇组,对照组细胞不做处理,白藜芦醇组细胞加入50μmol·L^(-1)白藜芦醇处理,激动剂组细胞加入1μg·mL^(-1)脂多糖(LPS)刺激,激动剂+白藜芦醇组细胞加入LPS 1μg·mL^(-1)刺激12 h后再用50μmol·L^(-1)白藜芦醇预处理12 h,MTT法检测细胞存活率,流式细胞仪检测细胞凋亡率,ELISA检测白细胞介素(IL)-6、IL-1β、肿瘤坏死因子α(TNF-α)含量,Transwell实验检测细胞侵袭能力以及蛋白印迹法检测上皮钙黏蛋白(E-cad)、神经钙黏蛋白(N-cad)、波形蛋白(vimentin)和p-p65蛋白相对表达量。结果与对照组比较,白藜芦醇组细胞存活率、IL-6、IL-1β、TNF-α含量以及N-cad、vimentin和p-p65蛋白相对表达量降低,侵袭细胞数减少,细胞凋亡率和E-cad蛋白相对表达量升高,激动剂组细胞存活率、IL-6、IL-1β、TNF-α含量以及N-cad、vimentin和p-p65蛋白相对表达量升高,侵袭细胞数增多,细胞凋亡率和E-cad蛋白相对表达量降低(P<0.05);与白藜芦醇组比较,激动剂+白藜芦醇组细胞存活率、IL-6、IL-1β、TNF-α含量以及N-cad、vimentin和p-p65蛋白相对表达量升高,侵袭细胞数增多,细胞凋亡率和E-cad蛋白相对表达量降低(P<0.05);与激动剂组比较,激动剂+白藜芦醇组细胞存活率、IL-6、IL-1β、TNF-α含量以及N-cad、vimentin和p-p65蛋白相对表达量降低,侵袭细胞数减少,细胞凋亡率以及E-cad蛋白相对表达量升高(P<0.05)。结论白藜芦醇可抑制脑胶质瘤细胞增殖和侵袭、促进其凋亡,其可能是通过抑制NF-κB信号通路减轻炎症反应、抑制上皮间质转化发挥调控作用的。展开更多
基金National Natural Science Foundation of China(grant numbers 82174143)the Innovative Team Project of Ordinary Universities in Guangdong Province(grant numbers 2022KCXTD016).
文摘Background:Liu-Jun-Zi decoction(LJZD),a classical nourishing formula in China,has been proven to be effective in treating chemotherapy-induced anorexia.In this study,the mechanism of LJZD in alleviating chemotherapy-induced anorexia was discussed from the aspects of regulating gut microbiota,repairing intestinal barrier injury and inhibiting inflammatory pathways.Methods:A rat model of chemotherapy-induced anorexia was established using cisplatin.The study evaluated the therapeutic effects of LJZD by observing the weight,food intake,and intestinal pathology of rats.The impact of LJZD on gut microbiota and metabolites,specifically short-chain fatty acids,was investigated through gut microbiota analysis and targeted metabolomics.The anti-inflammatory and intestinal protective effects of LJZD were assessed by examining the expression of intestinal tight junction proteins associated with the inflammatory pathway.Results:LJZD alleviated cisplatin-induced inflammation and intestinal barrier disruption,as evidenced by upregulated expression of tight junction protein 1(TJ-1)and occludin,along with reduced serum levels of interleukin 6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and lipopolysaccharide.Additionally,LJZD alleviated microbiota imbalance and regulated the levels of short-chain fatty acids,especially increased the relative abundance of Coriobacteriales Incertae Sedis,Lactabacillus johnsonii F19785,Parasutterella,and reduced the Tyzzerella.In the hypothalamus,LJZD exerts suppressive effects on the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)p65 signaling pathway,leading to a downregulation in the transcriptional activity of IL-6 and IL-1β,as well as Interleukin 6 receptors(IL-6R)and Interleukin-1βreceptors(IL-1R1)mRNA expression levels.Conclusion:In summary,LJZD alleviate chemotherapy-induced anorexia by modulating the gut microbiota,repairing the intestinal mechanical barriers,and suppressing the TLR4/MyD88/NF-κB p65 signaling pathway.
